Novel LCA5 mutation causes Retinitis pigmentosa

Introduction: A consanguineous Bedouin family presented with a phenotype of Leber Congenital Amaurosis (LCA) affecting an individual at the latest generation in an apparent recessive mode of inheritance. Materials and Methods: Whole exome sequencing data of an affected individual were analyzed and filtered for known benign variants using our in-house databases along with open access databases (1000 genomes, NHLBI ESP, ExAC). Results: The analysis yielded several candidate variants in genes previously associated with various ocular disorders. Among candidate variants, a novel homozygous missense p.K391* mutation in Leber Congenital Amaurosis 5 (LCA5) was the only one in a gene previously associated with LCA. The mutation was verified by Sanger sequencing and was found to be fully segregate in the affected kindred as expected for recessive heredity. Furthermore, the mutation was not found in 100 healthy ethnically-matched controls. In-silico analysis of the p.K391* variant showed that it is likely to have a deleterious effect on the mature protein. Conclusions: Mutations in LCA5 were previously described as causative for conditions such as Retinitis pigmentosa and Leber Congenital Amaurosis. Our data suggest that the novel LCA5 homozygous mutation is the cause for the autosomal recessive, isolated, inherited LCA in this kindred.